The proposed project will investigate the role of prostaglandins (PGs) and other products of polyunsaturated fatty acid metabolism in inflammatory diseases in man. A new kinetic mechanism for the regulation of PG synthesis is studied in rheumatoid synovival cells, and a PG-stimulating factor from rheumatoid synovial cells is described. The regulation of PG synthesis by alterations in the fatty acid composition in human cells in tissue culture, especially the effects of addition of all-cis 5,8,11,14,17 eicosapentaenoic acid (EPA) will be studied, providing a basis for nutritional alternations of PG and leukotriene synthesis. The production of leukotrienes and other lipoxygenase products by rheumatoid synovial tissue and cells in vitro will be investigated, and a new chemotactic factor from rheumatoid synovia will be characterized. The alteractions in bone resorption in vitro by factors from rheumatoid synovial tissue and the modification of bone resorption activity by EPA-induced changes in PG metabolism should contribute to better understanding of bone destruction in rheumatoid arthritis and in enoplastic diseases. Diets enriched with EPA are shown to protect (NZB x NZW) F(1) mice from the development of glomerulonephritis, a model for the renal disease of systemic lupus erythematosis, and proposed studies will investigate the mechanism of protection. Dietary EPA also leads to elevated IgE and IgG levels in rats, and augments some of their associated immunologic reactions. The proposed study of the altered immunologic and inflammatory reactions in animals by EPA-enriched diets should provide a new basis for alteractions of inflammatory and allergic disease states in man, by nutritional changes in dietary fatty acids.